kolodkin6

v_1

v_1

NRLn + RE = REL

v_2

v_2

Lc = Ln_

v_3

v_3

Ln_ + NR = NRLn

v_4

v_4

NRc = NRLc

v_5

NRc = {3.44444444444444}NR

v_6

v_6

NRLc = {3.44444444444444}NRLn

Global parameters

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


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Design principles of nuclear receptor signaling: how complex networking improves signal transduction.

  • Alexey N Kolodkin
  • Frank J Bruggeman
  • Nick Plant
  • Martijn J MonĂ©
  • Barbara M Bakker
  • Moray J Campbell
  • Johannes P T M van Leeuwen
  • Carsten Carlberg
  • Jacky L Snoep
  • Hans V Westerhoff
Mol. Syst. Biol. 2010; 6 : 446
Abstract
The topology of nuclear receptor (NR) signaling is captured in a systems biological graphical notation. This enables us to identify a number of 'design' aspects of the topology of these networks that might appear unnecessarily complex or even functionally paradoxical. In realistic kinetic models of increasing complexity, calculations show how these features correspond to potentially important design principles, e.g.: (i) cytosolic 'nuclear' receptor may shuttle signal molecules to the nucleus, (ii) the active export of NRs may ensure that there is sufficient receptor protein to capture ligand at the cytoplasmic membrane, (iii) a three conveyor belts design dissipating GTP-free energy, greatly aids response, (iv) the active export of importins may prevent sequestration of NRs by importins in the nucleus and (v) the unspecific nature of the nuclear pore may ensure signal-flux robustness. In addition, the models developed are suitable for implementation in specific cases of NR-mediated signaling, to predict individual receptor functions and differential sensitivity toward physiological and pharmacological ligands.

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